Resolution of apolipoprotein A1 and A2 proteoforms: their cardiometabolic correlates and implications for future research

John T. Wilkins, Anand Rohatgi

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations


Purpose of reviewA 'proteoform' is defined as one specific protein structural form that results from the combination of allelic variation, alternative RNA splicing, and/or posttranslational modifications (PTMs) in specific locations on the amino acid backbone. Apolipoproteins A1 and A2 are highly abundant apolipoproteins that mediate HDL structure and function. ApoA1 and apoA2 are known to undergo PTMs, which results in multiple proteoforms. However, the catalogue of apoA1 and apoA2 proteoforms as well as their associations with cardiometabolic health characteristics has not been described until recently. In this brief review, we discuss recent efforts to catalogue the spectrum of apoA1 and apoA2 proteoforms, to understand the relationships between the relative abundance of these proteoforms with cardiometabolic phenotypic characteristics, and we will discuss the implications of these findings to future research.Recent findingsA broad spectrum of apoA1 and apoA2 proteoforms has been characterized. Although, the types of apoA1 and A2 proteoforms are consistent across individuals, the relative abundances of proteoforms can vary substantially between individuals. Proteoform-specific associations with cardiometabolic characteristics in humans, independent of absolute apolipoprotein abundance, have been described. These recent findings suggest multiple levels of protein structural variation that arise from known and unknown metabolic pathways may be important markers or mediators of cardiometabolic health.SummaryUnderstanding the associations between apolipoprotein proteoforms and phenotype may lead to enhanced understanding of how apolipoproteins mediate lipid metabolism and affect atherosclerotic cardiovascular disease (ASCVD) risk, which may lead to discovery of novel markers of risk and/or key mechanistic insights that may drive further druggable targets for modifying lipid metabolism and reducing ASCVD risk.

Original languageEnglish (US)
Pages (from-to)264-269
Number of pages6
JournalCurrent opinion in lipidology
Issue number4
StatePublished - Aug 1 2022


  • apolipoprotein A1
  • apolipoprotein A2
  • cardiometabolic health
  • proteoform

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics
  • Molecular Biology
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism
  • Cell Biology


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